Short-Chain Fatty Acids Impair Neutrophil Antiviral Function in an Age-Dependent Manner

Area of Science:

• Immunology
• Microbiology
• Women's Health

Background:

• Half of people living with HIV (PLWH) are women, with younger women disproportionately affected.
• The vaginal microbiome and its metabolites, like short-chain fatty acids (SCFAs), influence HIV risk.
• SCFAs modulate neutrophil function, but their impact on anti-HIV responses is unclear.

Purpose of the Study:

• To investigate how SCFAs alter neutrophil function and anti-HIV responses in younger and older women.
• To determine if SCFA-induced changes in neutrophils differ between age groups.

Main Methods:

• Blood neutrophils from younger and older women were treated with SCFAs (acetate, butyrate, propionate).
• Neutrophil phenotype, migration, and anti-HIV activity (NET release, defensin release, chemokine secretion) were evaluated.
• SCFA concentrations mimicked those found during bacterial vaginosis.

Main Results:

• SCFAs induced phenotypical changes in neutrophils, particularly in older women.
• Butyrate and propionate altered neutrophil activation and survival markers.
• Acetate and butyrate inhibited neutrophil migration; SCFAs reduced anti-HIV defensin release in older women.
• SCFA treatment delayed neutrophil extracellular trap (NET) release and dampened chemokine secretion post-HIV stimulation.

Conclusions:

• SCFAs can impair neutrophil-mediated innate anti-HIV immunity.
• Age influences SCFA-induced alterations in neutrophil function.
• Findings highlight SCFAs as potential modulators of HIV risk in women.